Specific Aims
The Problem of Transitions Between Formulas for Infants. At one time or another, many infants experience feeding difficulties that can vary from mild fussiness to diet rejection. Typically, feeding disruptions last only for a few days and are of little consequence. But, for a number of infants who must, for one reason or another, make a transition between diets, from mothers' milk to formula, or from one formula to another, there can be more profound food rejection resulting from the diet transition. Such problems can be particularly severe in infants who must change to special diets that provide specific supplementation (Hoekelman et al., 1997). Such infants often resist pediatricians' and parents' attempts to introduce these therapeutic diets, apparently rejecting diets because they are novel or distasteful (e.g. Hauser et al., 1993). This unwillingness to consume the special formula can create distress and anxiety for parents and can result in a further deterioration of the infant's condition. Sometimes the problems can be so severe they require the use of intragastric or intravenous feeding and expensive hospital care.
Significance
The Diet Transition Problems of Infants. Infants are frequently required to switch from one diet to another. These transitions occur because of convenience, aesthetics, economics, or, in the most challenging situations when they are medically indicated. The transition can be from breast to bottle or from one bovine-based formula product to another. Sometimes it is from a standard formula to a specialized diet specifically formulated for a particular metabolic problem (Benson & Masor, 1994; Sampson, James, & Bernhisel-Broadbent, 1992). These diet transitions can be difficult for infants and the parents because infants may show mild to vigorous rejection of the new diet or feeding mode (Hauser et al., 1993). The present invention is oriented toward facilitating these diet transitions by improving the acceptance or preference for the new diet. This product should have a broad utility and be helpful even when only mild difficulties are to be expected. However, testing and product development is also oriented to situations where medical need dictates a diet transition and in which there is a recognized reluctance of infants to make a smooth diet transition.
The most common medical indication for a diet transition is a suspected allergy to proteins in bovine-based formulas (Host & Halken, 1990; Sampson, et al., 1992; Hoekelman et al., 1997). Formula companies market several soybean-based diets (our current market survey shows approximately 30% of formula offered on market shelves to be soy-based) to address this problem. They are not as sweet as cow or human milk, but the manufacturers have worked hard to make the taste and odor of these diets acceptable to infants (and their parents). There is usually resistance to this formula transition, though eventually babies will adjust to these soy diets and consume them.
To avoid allergic reactions, some babies need a predigested formula (Benson & Masor, 1994; e.g., Alimentum.TM., Nutramigen.TM., Pregestimil.TM.) in which short peptides or amino acids replace the protein source. These diets taste bad to adults (and apparently to infants) and with these diets resistance to the diet transition can be much greater.
Finally, some babies are born with metabolic abnormalities, usually in the metabolism of a specific amino acid (e.g. homocystein, or phenylalanine, or valine). These infants need to be fed a formula that is specially constructed to deal with the problem (e.g. a phenylalanine free formula such as Lofenelac for phenylketonuria). These diets, apparently, are also very unpleasant to infants and can be difficult to get the infants to consume. These infants are already often in a state of poor nutrition which can be compounded by the problem of the diet transition. In extreme cases the difficulties can be severe enough to require hospitalization along with i.v. or i.g. diet supplementation. Thus, for a number of medical reasons ranging from allergic reactions to cows milk to metabolic disorders, many infants must be switched from their parents' original formula choice to a formula that addresses the infants special needs (e.g., soy-based formula for infants allergic to cow's milk). Very early (within the first one to four weeks) this change may present little difficulty to the infant and the caregiver. However, after about six weeks a change in the infants' diet can result in a significant amount of stress to the infant who may resist this change and produce profound anxiety in the caregiver attempting to implement the change.
Basic Research on Early Appetitive Learning. The application of the present invention to infant feeding problems is based on two fundamental phenomena. The first is the phenomenon of "conditioned appetite". Wiengarten (1984) and others have provided an important demonstration in adult animals that stimuli or signals paired with feeding can themselves come to induce ingestion. The effect is powerful enough that it will induce feeding even in animals that are sated (Weingarten, 1984). Although we have been aware since Pavlov that conditional stimuli (CS's) can cause a hungry animal to anticipate feeding (i.e., bell.fwdarw.salivation), conditioned appetitive CS's go beyond anticipatory conditioning in controlling ingestive behavior itself, inducing eating and influencing diet preference. The present application makes use of the possibility of conditioning appetites to an odor CS in infants and using this CS to transfer ingestion to another diet.
The second basis for the present invention method is the revelation over the last 15 years that infant mammals, including humans, are capable of remarkable appetitive learning (see reviews by Hall & Oppenheim, 1981; Spear & Rudy, 1991). In retrospect, it may seem somewhat surprising, but before the recent era of learning-development studies in animals and human infants, newborns were, with a few exceptions, viewed as deficient in learning capabilities, only showing learning to a very limited degree, and only when strong aversive stimuli were used. However, beginning in the early 1980s, studies in neonatal rodents and humans have shown that infants are capable of impressive and often complex learning and conditioning, and that such learning is likely to play a role in their ongoing behavior and to continue to influence their behavior throughout life.
Experiments in developing rodents are particularly relevant to our proposed diet-transition technique. In 1979, Johanson & Hall showed that one-day-old rat pups would learn to probe into soft paddles over their heads in order to receive milk infusions into their mouths. Most importantly, they would learn to distinguish between two paddles (one providing a milk infusion, the other not) on the basis of an odor on the paddle; the odor itself comes to evoke an appetitive response. Thus, infant rodents born in an even less developed stage than humans, are capable of odor-based appetitive learning from the time of birth. This study and others like it provoked a flurry of investigations of learning in very young mammals over the last 15 years. Such studies culminated in work showing learning as early as late fetal stages in rodents and humans (Fifer, 1987; Stickrod, Kimble, & Smotherman, 1982) and have established beyond doubt the remarkable learning capabilities of neonates.
From the point of view of the present application, the most relevant prior art is a series of studies in developing rodents showing conditioned appetites from very early ages using olfactory stimuli. When odor conditioned stimulus (CS)'s are pared with milk infusions into the mouths of rat pups, pups develop conditioned preferences for the odors (Johanson & Hall, 1982) and also develop conditioned mouthing responses (Johanson, Hall, & Polefrone, 1984). The learning is robust. It occurs with relatively few pairings (5 to 15) and is long lasting (&lt;one week). It is also specific to the odor CS that is used. Most importantly, in infant rodents, conditioned odor CS have been shown to be capable of influencing ingestion of non-referred solutions in a paradigm parallel to the application we are describing here (Johanson & Terry, 1984). Thus, odor conditioning in infant mammals can work to influence appetitive behavior and ingestion.
Note that that odors work well as stimuli in these studies because they are particularly appropriate signals for conditioning in infants. Olfaction is one of the sensory dimensions to which infant mammals are most attuned because of its role in suckling. The olfactory system is operable very early (Alberts, 1984) and has been shown to be important in guiding suckling behavior in numerous species including rats (Feicher & Blass, 1997), cats (Rosenblatt, 1971), and humans (Schaal, 1988). Odors are also naturally and readily linked with the act of ingestion (Rozin, 1982). Thus, they provide particularly good cues for use in influencing diet transitions. The present invention teaches an applied method of managing olfactory stimuli in the suckling situation.
Studies in Human Infants Showing Presence of Relevant Mechanisms. For human infants, there are no comparable studies on a direct influence of olfactory conditioning on feeding. However, it is expected that the appetitive conditioning phenomenon is likely to generalize to other mammals including humans. Below are listed other factors which indicate that the present invention can improve human diet transitions.
First, we can be sure that taste and olfactory responsiveness are comparably well developed in rodents and humans. As has been shown in the compelling photographic documentation and analysis of Steiner (1977), from the day of birth, newborn humans are quite expressive with regard to their early appreciation of sweet and bitter tastes (also Desor, 1973). Responsiveness to odors is well developed in infants as well. Infants have been observed to respond to a range of artificial food odors prior to their first feeding (Steiner, 1977; also Engin, Lipsitt, & Kaye, 1963). Of particular relevance is the demonstration that infants may have intrinsic differential responsiveness to olfactory stimuli, with some stimuli being more preferred than others (Makin & Porter, 1989; Porter, Makin, Davis, Christensen, 1991).
Second, studies of learning and conditioning in human neonates have confirmed that the same general mammalian capabilities exist as described for other mammals above. In one of the early demonstrations before the modern era, Marquis (1931) demonstrated that sucking responses were capable of being conditioned by pairing a buzzer with the presentation of the infant's bottle. Instrumental conditioning of sucking has also been demonstrated (e.g. Kron, 1968). A good example of more recent work is that of Blass, Ganchrow, and Steiner (1984) showing that in newborn babies a small amount of sucrose squirted into the mouth will induce appetitive responses that can be conditioned to a tactile stimulation of the forehead. Blass's studies have also demonstrated a parallel neurobiological substrate for the reinforcement mechanisms in human and rodent infants (Blass, 1990), providing a further generalization across species.
Third, it is known that odors work well as learning signals in human infants. Infants who received odor stimuli paired with a form of gentle stroking showed head-turning and preference for the odor on the next day (Sullivan et al., 1991). The preferences were specific for the odor that received the conditioning. Conditioned preference was true for infants that were in a variety of behavioral states at the time of training and testing. More generally, infants are quick to learn about the olfactory characteristics of stimuli in their world and recognize the odors of their parents (feeders) with little experience (Porter, et al., 1991). Thus, while there are no specific demonstrations of conditioned olfactory modulation of ingestion in humans, there is ample indication that such conditioning is likely to work, as it does in animals.
We should point out that for human babies, introducing additional olfactory stimuli in the feeding situation should not be viewed as creating an unnatural form of stimulation or experience. During normal breast feeding, infants experience a range of olfactory stimulation or experience including olfactory stimulation from the mother's skin. In addition, breast milk contains the odors of foods the mother has recently ingested (Mennella & Beauchamp, 1994; Mennella, 1995). Breast-feeding thus provides a rich array of olfactory experience and variation in diet flavor. By contrast, formula-feeding can be viewed as a relatively monotonous flavor alternative for infants; an unnaturally impoverished one.
The present invention teaches the placement of an absorbent dot on a feeding container at a location which will place the dot near the user's nasal passages during feeding. The dot is filled with an odorant before feeding.